The proposed research is designed to study: 1) the genetics and immunology of the Hemopoietic-histocompatibility (Hh) system, that is, the H-2 linked genetic controls of tissue-specific Hh membrane structures selectively expressed on hemopoietic cells; 2) immune responsiveness and mechanisms of unresponsiveness to such antigenic structures; 3) the role of the Hh genes associated with subregions of the major histocompatibility complex in resistance to bone marrow allografts, orderly stem cell proliferation and differentiation (hemopoiesis). The primary goal is to test the hypothesis that Hh gene products are a new class of polymorphic cell-surface differentiation antigens recognizable by autologous or syngenetic as well as allogeneic cells of the immune system. Experiments will be performed in vivo (bioassays for resistance to graft proliferation and in vitro (natural cytotoxicity and induction of cell mediated immunity against Hh-bearing target cells) and designed so as to detect and quantitate variations of Hh-gene expression in stimulating and target cells, and variations of immunocompetence in responder animals or cells. Responder, effector and stimulator cells will also be defined by cell-surface markers. Antisera of restricted specificity (e.g., anti-Ia, anti-H-2D, etc.) will be tested for the ability to prevent stimulation or effector:target cell interaction. The dependence of anti-Hh-reactions on macrophage and lymphocyte subpopulations will be studied both in vivo and in vitro.